There is accumulating experimental evidence from our laboratory and others that solid tumors are angiogenesis-dependent. Our observation that heparin can promote angiogenesis but cannot initiate it has led to two new findings: (1)\hexasaccharide fragment of heparin applied with hydrocortisone or cortisone inhibits angiogenesis in the chick embryo, the rabbit cornea, and in some tumor-bearing mice. In certain animal-tumor systems, when heparin is ingested orally and cortisone acetate given parenterally, there is tumor regression and decrease of metastases to less than 0.1% of controls. Other tumors are nonresponsive to the doses of heparin and cortisone used. (2)\In a second set of experiments, heparin-affinity chromatography was used to purify to homogeneity a tumor-derived mitogen for capillary endothelial cells that also is a potent angiogenic factor. The factor was purified approximately one million-fold and has a Mr = 18,000 and a pI of 9.8. It stimulates proliferation of capillary endothelial cells in vitro half-maximally at 1 ng/ml and stimulates angiogenesis in the chick embryo at approximately 120 ng with virtual absence of inflammatory cells. These studies provide further evidence that angiogenesis is a critical control point in the progressive growth of solid tumors. (J)